C.15

Question 1

Macrolides, Pleuromutillins

Answer 1

1. Macrolides: Clarithromycin,
   Roxithromycin,
   Azithromycin,
2. Pleuromutillins: Lefamulin

Question 2

Macrolides

Answer 2

MOA: Bacteriostatic (bactericidal) action.
Binds to the 50S subunit→ blocks translocation and the formation of the initiation complex.
Non-antimicrobial immunomodular properties (Decreases neutrophils and inflammatory cytokines);
Spectrum: Therapeutically most relevant → Intracellular bacteria (mycoplasma, chlamydia, ureaplasma, legionella), Gram positive cocci (Pneumococci, streptococci, staphylococci); Additionally sensitive bacteria → some gram (-) (campylobacter, helicobacter, neisseria, haemophilus), treponema, corynebacteria, atypical mycobacteria;
Resistance due to: Efflux, Reduced permeability, Modification of the ribosomal Binding site → MLSB resistance;
IND: Respiratory or other infections with IC bacteria, As penicillin substitutes, Helicobacter eradication, campylobacter enteritis, corynebacterium, bordetella infections, atypical mycobacterial infections;
Pharmacokinetics:
-Erythromycin (→ Destroyed by gastric acid (enteric coating or esterified), Wide distribution, NOT BRAIN, Short T1/2 (4x/day) (liver-bile);
-Newer substances (→ Acid-stable, Longer T1/2 , 1-2x/day, High level → taken up in leukocytes, macrophages → stronger effect, short therapy);
SEs: Newer drugs have less!
→ GI pain, nausea, vomiting, anorexia (→ especially erythromycin) → motilin like property, Rarely allergy or liver problems;
Drug interactions: The 14 membered-ring macrolides → hepatic enzyme inhibitors → increased levels of theophylline, oral anticoagulants, antihistamines, statins.
-Azitromycin and dirithromycin → no inhibition of enzymes (No 14-membered ring)

Question 3

Clarithromycin

Answer 3

Spectrum/IND: Similar to general info, Prophylaxis against M. Avium, H. Pylory eradication regimen (Triple therapy + Amo + PPI);
Pharmacokinetics: Hepatic metabolism or renal elimination of intact drug, Inhibitor of CYP450 enzymes;
Resistance due to: Methylation of ribosomal binding site, Efflux pump, Drug-metabolising esterase enzymes (Enterobacteriaceae),
-Cross-resistance with clindamycin and streptogramin;
SEs: GI distress (motilin receptor stimulation → enhanced peristalsis), Ototoxicity (at high doses), Skin rash, Eosinophilia, QT prolongation, Acute cholestatic hepatitis (generally rare, more common with erythromycin)

Question 4

Roxithromycin + Erythromycin

Answer 4

Erythromycin (natural),
Roxithromycin (semi-synthetic);
Spectrum/IND: Similar to the general info, Bordetella pertussis 1st choice!(treatment and prophylaxis), Community aquired pneumonia - atypical p.;
NO activity against: MRSA and PRSP;
Pharmacokinetics: p.o administration, Biliary elimination, Inhibitor of CYP450 enzymes, Prokinetic;
Resistance due to: Methylation of ribosomal binding site, Efflux pump, Drug-metabolising esterase enzymes (Enterobacteriaceae),
-Cross-resistance with clindamycin and streptogramin;
SEs: GI distress (motilin receptor stimulation → enhanced peristalsis), Ototoxicity (at high doses), Skin rash, Eosinophilia, QT prolongation, Acute cholestatic hepatitis (generally rare, more common with erythromycin)

Question 5

Azithromycin

Answer 5

Semisynthtetic;
Spectrum/IND: More effective for Gram negatives→ H. Influenza, Neisseria, M. Catarrhalis, Urogenital infections caused by Chlamydia (single dose), Corynebacterium diphteria;
NOT effective for: UTIs;
Pharmacokinetics: Absorption impeded by food, Reaches high intracellular concentrations (e.g. Phagocytes), Renal elimination as intact drug; T1/2: 2-4 days;
SEs: GI distress (motilin receptor stimulation → enhanced peristalsis), Ototoxicity (at high doses), Skin rash, Eosinophilia, QT prolongation, Acute cholestatic hepatitis (generally rare, more common with erythromycin)

Question 6

Lefamulin

Answer 6

MOA: bactericidal, inhibits 50S subunit of the ribosome: has a unique induced-fit type of action that closes the binding pocket within a ribosome, conferring close contact of the drug to its target, therefore improving therapeutic efficacy → less likely cross-resistance;
IND/Spectrum: designed for CAP → S. Pneumonia, S. Aures, Legionella pneumonia, H.influenza, Chlamydophila pneumonia, mycoplasma pneumonia;
NOT effective against: E. faecalis, G (-) rods;
Pharmacokinetics: administered p.o/i.v, good absorption, 25% Bioavailability, Should not be administered with food (1 hour before or 2 hours after), Distributes mainly to the lung tissues, Metabolised by CYP3A4 in the liver, Mainly excreted by the GI tract, and some in the kidney, Not removable by dialysis;
Active metabolite; T1/2: 8 hours;
SEs: GI distress (motilin receptor stimulation → enhanced peristalsis), Ototoxicity (at high doses), Dry mouth, Irregular heartbeat, QT prolongation, Acute cholestatic hepatitis (generally rare, more common with erythromycin)

Question 7

Spiramycin

Answer 7

Special spectrum and indication: Toxoplasmosis in pregnancy

Question 8

Pleuromutilins

Answer 8

antibiotics that selectively inhibit bacterial translation and are semisynthetic derivatives of the naturally occurring tricyclic diterpenoid pleuromutilin, which received its name from the pleuromutilin-producing fungus Pleurotus mutilus.

Question 9

Theophylline

Answer 9

used to prevent and treat wheezing, shortness of breath, and chest tightness caused by asthma, chronic bronchitis, emphysema and other lung diseases. It relaxes and opens air passages in the lungs, making it easier to breath